Association of RAGE Gene Polymorphism (rs2070600, G82S) With Diabetic Retinopathy Among Type 2 Diabetes Mellitus Patients in a South Indian Population: A Hospital-Based Case-Control Study

Background: Diabetic retinopathy (DR) is one of the leading microvascular complications associated with type 2 diabetes mellitus (T2DM), yet its occurrence varies among patients with similar metabolic exposure, suggesting genetic modifiers. The AGE-RAGE axis is mechanistically linked to oxidative stress and inflammatory signalling in retinal injury, and the functional AGER/RAGE rs2070600 (G82S) variant is a plausible susceptibility locus. Objective: To evaluate the association of rs2070600 (G82S) with DR in a South Indian T2DM. Methods: A Total of 220 adults with T2DM were recruited (110 DR; 110 non-DR). DR status was confirmed by ophthalmologist examination/imaging. Biochemical profiling included glycaemic indices and lipids. rs2070600 was genotyped by PCR-RFLP with sequencing-based quality control. Results: DR cases had longer diabetes duration, higher PPBS and HbA1c, and an atherogenic lipid tendency. Genotype distributions differed (p<0.001) with A-allele enrichment in DR (0.50 vs 0.305). Compared with GG, AG (OR 4.12, 95% CI 2.19-7.78) and AA (OR 3.26, 95% CI 1.57-6.80) increased DR odds; the dominant model was significant, while the recessive model was not. Controls deviated from the Hardy-Weinberg equilibrium (HWE). Conclusion: rs2070600 (G82S) is associated with DR susceptibility in this South Indian T2DM sample, supporting larger multicentre studies with multivariable adjustment and soluble RAGE phenotyping.